Dr. Reinholdt earned her Ph.D. in Genetics from University of Connecticut, Department of Molecular and Cellular Biology. She conducted her graduate work with Dr. Hallie Krider – a laboratory largely focused on the role of heterochromatin in fertility and development using Drosophila, as well as other insect and mammalian models. Dr. Reinholdt’s work demonstrated that development of anucleate sperm, a normal, developmentally programmed event in Lepidoptera (moths and butterflies) is preceded by an aberrant meiotic prophase in which holocentric meiotic chromosomes fail to synapse and recombine.
As a post doctoral fellow with Drs. John Schimenti and Mary Ann Handel, Dr. Reinholdt went on to pursue the underlying mechanisms regulating chromosome pairing and recombination in mammals using forward genetic approaches. As part of the Reprogenomics ENU program (now the The JAX Center for Genetics of Fertility and Reproduction) at The Jackson Laboratory, Dr. Reinholdt led efforts to clone several ENU alleles responsible for aberrant meiotic chromosome dynamics including alleles of Rec8, Smc1beta, and Prdm9.
Since establishing her laboratory at The Jackson Laboratory in 2008, Dr. Reinholdt has pioneered the use of high throughput sequencing for the discovery of spontaneous mutations underlying Mendelian disease phenotypes in mice (D’Ascenzo, 2009; Fairfield, 2011; Fairfield, 2015). These efforts led to the discovery of new mutations in over 100 spontaneous models of Mendelian disease and the birth of a new resource program “Resources for Comparative Mendelian Genomics”.
Dr. Reinholdt’s laboratory also developed approaches for the derivation of mouse embryonic stem cells from any mouse strain, including strains previously deemed recalcitrant (Reinholdt et al., 2012; Czechanski et al., 2014) including NOD and NSG. Her group continues to utilize these approaches to develop novel mES cell lines and iPS cells from specific disease models (Alzheimer’s models, Down syndrome, Turner syndrome, etc.).
Dr. Reinholdt’s research program radiates from a core interest in the etiology of aneuploidy, both in the germline and in the soma. In her efforts to discover the genes required for normal germline development and fertility, she has found that the germline is exquisitely sensitive to mutations in components of the mitotic spindle that lead to aneuploidy (Czechanski et al., 2015), a sensitivity that may also extend to embryonic and adult stem cells. Cell type-specific mechanisms for maintenance of genome integrity have not been explained. Dr. Reinholdt’s work has demonstrated that the sensitivity of the germline to cell cycle perturbations (i.e. through mutations in mitotic kinesins and kinetochore / centromere proteins) differs across inbred strains of mice, providing a unique opportunity to use mouse genetics to discover the underlying pathways governing cell division and survival across a variety of cell types.
The home of Dr. Reinholdt’s laboratory continues to be the The Jackson Laboratory, an independent nonprofit organization leveraging eight decades of expertise in genetics and genomics to increase understanding of human disease and discover precise genomic solutions.
As always, your interest and feedback are welcome.